20-890327-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_015985.4(ANGPT4):c.351G>A(p.Glu117=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,613,562 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0059 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00062 (10 hom.)
• Consequence: ANGPT4 NM_015985.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.65

Genes affected

ANGPT4 (HGNC:487): (angiopoietin 4) Angiopoietins are proteins with important roles in vascular development and angiogenesis. All angiopoietins bind with similar affinity to an endothelial cell-specific tyrosine-protein kinase receptor. The mechanism by which they contribute to angiogenesis is thought to involve regulation of endothelial cell interactions with supporting perivascular cells. The protein encoded by this gene functions as an agonist and is an angiopoietin. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 20-890327-C-T is Benign according to our data. Variant chr20-890327-C-T is described in ClinVar as [Benign]. Clinvar id is 710866.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.64 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00588 (896/152294) while in subpopulation AFR AF= 0.0202 (840/41556). AF 95% confidence interval is 0.0191. There are 6 homozygotes in gnomad4. There are 430 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANGPT4	NM_015985.4	c.351G>A	p.Glu117=	synonymous_variant	2/9	ENST00000381922.5
ANGPT4	NM_001322809.2	c.351G>A	p.Glu117=	synonymous_variant	2/8
ANGPT4	XM_011529239.4	c.310-1888G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANGPT4	ENST00000381922.5	c.351G>A	p.Glu117=	synonymous_variant	2/9	1	NM_015985.4	P1

Frequencies

GnomAD3 genomes AF: 0.00583 AC: 887 AN: 152176 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0201

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00573

GnomAD3 exomes AF: 0.00153 AC: 384 AN: 250868 Hom.: 2 AF XY: 0.00107 AC XY: 145 AN XY: 135632

Gnomad AFR exome AF: 0.0214

Gnomad AMR exome AF: 0.000898

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000618 AC: 903 AN: 1461268 Hom.: 10 Cov.: 32 AF XY: 0.000512 AC XY: 372 AN XY: 726948

Gnomad4 AFR exome AF: 0.0225

Gnomad4 AMR exome AF: 0.00107

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000809

Gnomad4 OTH exome AF: 0.00149

GnomAD4 genome AF: 0.00588 AC: 896 AN: 152294 Hom.: 6 Cov.: 32 AF XY: 0.00577 AC XY: 430 AN XY: 74470

Gnomad4 AFR AF: 0.0202

Gnomad4 AMR AF: 0.00274

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00567

Alfa AF: 0.00251 Hom.: 1

Bravo AF: 0.00675

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 20, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.057
Dann	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs79320190; hg19: chr20-870970;